1A1R

HCV NS3 PROTEASE DOMAIN:NS4A PEPTIDE COMPLEX

Summary for 1A1R

• Entry DOI: 10.2210/pdb1a1r/pdb
• Descriptor: NS3 PROTEIN, NS4A PROTEIN, ZINC ION, ... (4 entities in total)
• Functional Keywords: viral protein, serine protease, nonstructural proteins, cofactor peptide, helicase
• Biological source: Hepatitis C virus; More
• Cellular location: Core protein p21: Host endoplasmic reticulum membrane ; Single-pass membrane protein . Core protein p19: Virion . Envelope glycoprotein E1: Virion membrane ; Single-pass type I membrane protein . Envelope glycoprotein E2: Virion membrane ; Single-pass type I membrane protein . p7: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Protease NS2-3: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Serine protease NS3: Host endoplasmic reticulum membrane ; Peripheral membrane protein . Non-structural protein 4A: Host endoplasmic reticulum membrane ; Single-pass type I membrane protein . Non-structural protein 4B: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Non-structural protein 5A: Host endoplasmic reticulum membrane; Peripheral membrane protein. RNA-directed RNA polymerase: Host endoplasmic reticulum membrane ; Single-pass type I membrane protein : P27958 P27958
• Total number of polymer chains: 4
• Total formula weight: 47008.85

Authors

Kim, J.L.,Morgenstern, K.A.,Lin, C.,Fox, T.,Dwyer, M.D.,Landro, J.A.,Chambers, S.P.,Markland, W.,Lepre, C.A.,O'Malley, E.T.,Harbeson, S.L.,Rice, C.M.,Murcko, M.A.,Caron, P.R.,Thomson, J.A. (deposition date: 1997-12-15, release date: 1998-06-17, Last modification date: 2024-02-07)

Primary citation

Kim, J.L.,Morgenstern, K.A.,Lin, C.,Fox, T.,Dwyer, M.D.,Landro, J.A.,Chambers, S.P.,Markland, W.,Lepre, C.A.,O'Malley, E.T.,Harbeson, S.L.,Rice, C.M.,Murcko, M.A.,Caron, P.R.,Thomson, J.A.
Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide.
Cell(Cambridge,Mass.), 87:343-355, 1996

PubMed Abstract: An estimated 1% of the global human population is infected by hepatitis C viruses (HCVs), and there are no broadly effective treatments for the debilitating progression of chronic hepatitis C. A serine protease located within the HCV NS3 protein processes the viral polyprotein at four specific sites and is considered essential for replication. Thus, it emerges as an attractive target for drug design. We report here the 2.5 angstrom resolution X-ray crystal structure of the NS3 protease domain complexed with a synthetic NS4A activator peptide. The protease has a chymotrypsin-like fold and features a tetrahedrally coordinated metal ion distal to the active site. The NS4A peptide intercalates within a beta sheet of the enzyme core.

PubMed: 8861917
DOI: 10.1016/S0092-8674(00)81351-3

Experimental method

X-RAY DIFFRACTION (2.5 Å)